In vitro hemocompatibility screening of a slippery liquid impregnated surface coating for extracorporeal organ support applications.

INTRODUCTION: Clot formation, infection, and biofouling are unfortunate but frequent complications associated with the use of blood-contacting medical devices. The challenge of blood-foreign surface interactions is exacerbated during medical device applications involving substantial blood contact area and extended duration of use, such as extracorporeal life support (ECLS). We investigated a novel surface modification, a liquid-impregnated surface (LIS), designed to minimize protein adsorption and thrombus development on medical plastics. METHODS: The hemocompatibility and efficacy of LIS was investigated first in a low-shear model with LIS applied to the lumen of blood incubation vials and exposed to human whole blood. Additionally, LIS was evaluated in a 6 h ex vivo circulation model with swine blood using full-scale ECLS circuit tubing and centrifugal pumps with clinically relevant flow rate (1.5 L/min) and shear conditions for extracorporeal carbon dioxide removal. RESULTS: Under low-shear, LIS preserved fibrinogen concentration in blood relative to control polymers (+40 ± 6 mg/dL vs polyvinyl chloride, p < .0001), suggesting protein adsorption was minimized. A fibrinogen adhesion assay demonstrated a dramatic reduction in protein adsorption under low shear (87% decrease vs polyvinyl chloride, p = .01). Thrombus deposition and platelet adhesion visualized by scanning electron microscopy were drastically reduced. During the 6 h ex vivo circulation, platelets in blood exposed to LIS tubing did not become significantly activated or procoagulant, as occurred with control tubing; and again, thrombus deposition was visually reduced. CONCLUSIONS: A LIS coating demonstrated potential to reduce thrombus formation on medical devices. Further testing is needed specialized to clinical setting and duration of use for specific medical target applications.

Dynamics of Confined Microgel Liquids: Weakened Spatial Confinement Effect by Microgel Particle Compliance.

Spatial confinement has a great impact on the structures and dynamics of interfacial molecular and polymer liquid films. Most prior research has focused on confined liquids of fixed material compliance and often treated them in approximation to the "hard-sphere" interaction model. In this study, we microscopically investigate the structural dynamics of highly deformable poly(N-isopropylacrylamide) (PNIPAM) microgels confined between two solid surfaces in comparison to that of nearly nondeformable microgels of the same chemistry. We observe that the mobility and structural relaxation of highly deformable PNIPAM microgels at an apparent volume fraction, ϕ = 0.49-0.70, show little change with the reduction of gap spacing, in stark contrast to confinement-induced dynamic retardation of "hard-sphere"-like stiff PNIPAM microgels. The critical gap spacing, defined as the onset of confinement effect to deviate from the bulk behavior, is found to be approximately 17-22 particle layers for highly deformable microgels of ϕ = 0.56-0.70, much smaller than that of approximately 40 particle layers or larger for stiff microgels or model "hard-sphere" colloidal liquids of similar ϕ. Additionally, we observe no evident confinement-enhanced structural reorganization of deformable microgels near the confining surfaces when gap spacing approaches the critical gap spacing. Microgel deformation upon strong confinement is attributed to the disrupted confinement-induced ordering of confined microgels. Hence, it is clearly indicated that spatial confinement exhibits a much weaker effect on highly compliant microgel particles than stiff ones, resulting in a significantly less reduction in microgel interfacial dynamics. It therefore gives insights into the molecular design of polymeric thin films of variable compliance to control friction and lubrication.

Hyperbaric polymer microcapsules for tunable oxygen delivery.

Over the past decade, there have been many attempts to engineer systems capable of delivering oxygen to overcome the effects of both systemic and local hypoxia that occurs as a result of traumatic injury, cell transplantation, or tumor growth, among many others. Despite progress in this field, which has led to a new class of oxygen-generating biomaterials, most reported techniques lack the tunability necessary for independent control over the oxygen flux (volume per unit time) and the duration of delivery, both of which are key parameters for overcoming tissue hypoxia of varying etiologies. Here, we show that these critical parameters can be effectively manipulated using hyperbarically-loaded polymeric microcapsules (PMC). PMCs are micron-sized particles with hollow cores and polymeric shells. We show that oxygen delivery through PMCs is dependent on its permeability through the polymeric shell, the shell thickness, and the pressure gradient across the shell. We also demonstrate that incorporating an intermediate oil layer between the polymeric shell and the gas core prevents rapid outgassing by effectively lowering the resultant pressure gradient across the polymeric membrane following depressurization.

Tunable Polymer Microcapsules for Controlled Release of Therapeutic Gases.

Encapsulation and delivery of oxygen, carbon dioxide, and other therapeutic gases, using polymeric microcapsules (PMCs) is an emerging strategy to deliver gas as an injectable therapeutic. The gas cargo is stored within the PMC core and its release is mediated by the physiochemical properties of the capsule shell. Although use of PMCs for the rapid delivery of gases has been well described, methods which tune the material properties of PMCs for sustained release of gas are lacking. In this work, we describe a simple method for the high-yield production of gas-in-oil-filled PMCs with tunable sizes and core gas content from preformed polymers using the sequential phase separation and self-emulsification of emulsion-based templates. We demonstrate that prolonged gas release occurs from gas-in-oil PMCs loaded with oxygen and carbon dioxide gas, each of which could have significant clinical applications.

Interfacial Nanoprecipitation toward Stable and Responsive Microbubbles and Their Use as a Resuscitative Fluid.

A new approach has been developed to prepare stable microbubbles (MBs) by interfacial nanoprecipitation of bioabsorbable polymers at air/liquid interfaces. This facile method offers robust control over the morphology and chemophysical properties of MBs by simple chemical modifications. This approach is amenable to large-scale manufacturing, and is useful to develop functional MBs for advanced biomedical applications. To demonstrate this, a MB-based intravenous oxygen carrier was created that undergoes pH-triggered self-elimination. Intravenous injection of previous MBs increased the risk of pulmonary vascular obstruction. However, we show, for the first time, that our current design is superior, as they 1) yielded no evidence of acute risks in rodents, and 2) improved the survival in a disease model of asphyxial cardiac arrest (from 0 to 100 %), a condition that affects more than 100 000 in-hospital patients, and carries a mortality of about 90 %.

Oxygen delivery using engineered microparticles.

A continuous supply of oxygen to tissues is vital to life and interruptions in its delivery are poorly tolerated. The treatment of low-blood oxygen tensions requires restoration of functional airways and lungs. Unfortunately, severe oxygen deprivation carries a high mortality rate and can make otherwise-survivable illnesses unsurvivable. Thus, an effective and rapid treatment for hypoxemia would be revolutionary. The i.v. injection of oxygen bubbles has recently emerged as a potential strategy to rapidly raise arterial oxygen tensions. In this report, we describe the fabrication of a polymer-based intravascular oxygen delivery agent. Polymer hollow microparticles (PHMs) are thin-walled, hollow polymer microcapsules with tunable nanoporous shells. We show that PHMs are easily charged with oxygen gas and that they release their oxygen payload only when exposed to desaturated blood. We demonstrate that oxygen release from PHMs is diffusion-controlled, that they deliver approximately five times more oxygen gas than human red blood cells (per gram), and that they are safe and effective when injected in vivo. Finally, we show that PHMs can be stored at room temperature under dry ambient conditions for at least 2 mo without any effect on particle size distribution or gas carrying capacity.

Control hydrogel-hyaluronic acid aggregation toward the design of biomimetic superlubricants.

Healthy synovial fluids (SFs) are complex fluids consisting of biopolymers, globule proteins, and lipids and regarded as superlubricants to provide nearly life-long low friction and wear protection of synovial joints in mammals. In this paper, we report that the intricate lubricious mixture can be simulated by the aggregation of hyaluronic acid (HA) and hydrogel particles in aqueous suspensions. In the HA aqueous suspensions added with synthetic polymer microgels, we have effectively captured the bulk rheological properties of healthy SFs. It is also confirmed by light scattering and fluorescence microscopic characterization that added hydrogel particles can enhance the HA network by hydrogel-mediated hydrogen bonding, leading to the fractal HA-hydrogel aggregating networks in aqueous suspensions. The potential application of HA-hydrogel particle aggregates as biomimetic superlubricants is supported by the comparable low friction at high load to that of healthy SFs.